Polyethylene Glycol (PEG) Versus Sennosides Study in Opioid-Induced Constipation in Cancer Patients

• Sponsor: British Columbia Cancer Agency (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01189409
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Duration (Months): 100
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is a study to compare the efficacy and tolerability of two laxatives for treatment of opioid-induced constipation in adult outpatients with cancer treated at the British Columbia Cancer Pain and Symptom Management/Palliative Care clinics. Each participating patient will be randomly assigned to one of two treatment groups.

Condition or Disease	Intervention/Treatment	Phase
Constipation; Cancer	Drug: PEG then Senna; Drug: Senna then PEG	Phase 4

Detailed Description

One group will be started on a bowel protocol of escalating doses of sennosides, plus a dummy polyethylene glycol (lactose), and the other will receive dummy sennosides capsules (lactose) plus polyethylene glycol, with the same dosing protocol. After three weeks of one active treatment the patients will switch to the alternate active product and dummy preparation. The total duration for the study will be 6 weeks for each patient.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: The primary outcome will be treated as a binomial outcome, expressed as the number of successful trials out of a pre-defined number of trials n = 18. Given this, the primary outcome will be analysed via a generalized mixed effects model. The model will include: (i) fixed effects for treatment, treatment period and their interaction, (ii) fixed effects for the baseline characteristics and (iii) a random patient effect. Including the latter effect in the model will help capture the within-patient correlation among the values of the primary outcome collected in Period I and Period II for the same patient. All statistical analyses will be conducted using the open-source statistical software package R.The primary outcome will be treated as a binomial outcome, expressed as the number of successful trials out of a pre-defined number of trials n = 18. Given this, the primary outcome will be analysed via a generalized mixed effects model. The model will include: (i) fixed effects for treatment, treatment period and their interaction, (ii) fixed effects for the baseline characteristics and (iii) a random patient effect. Including the latter effect in the model will help capture the within-patient correlation among the values of the primary outcome collected in Period I and Period II for the same patient. All statistical analyses will be conducted using the open-source statistical software package R.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Double blind using a dummy alternate treatment.
• Primary Purpose: Supportive Care
• Official Title: A Randomized, Double Blind, Double-dummy, 2-treatment, 2-period Crossover Comparison of Sennosides and Polyethylene Glycol in Treatment of Opioid-induced Constipation in Outpatients With Cancer
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PEG then Senna PEG in stepped bowel protocol	Drug: PEG then Senna; Stepped bowel protocol with PEG for 3 weeks followed by senna for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).; Other Names: Lax-a-Day
Experimental: Senna then PEG Stepped bowel protocol with Senna then PEG	Drug: Senna then PEG; Stepped bowel protocol with senna for 3 weeks followed by PEG for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).; Other Names: senokot

Outcome Measures

Primary Outcome Measures

1. Bowel Performance Scale (BPS) [Last 18 days of each 21 day study period]

   Mean values of Number of Days with Satisfactory Bowel Movements Per Days of Treatment across time by treatment, derived from the mixed effects Poisson regression model. If the BPS rating on a day was -1, 0 or +1, the patient's bowel movement on that day was deemed to be satisfactory.

Secondary Outcome Measures

1. Patient Preference [end of study (6 weeks)]

   The patients will be asked to state which treatment period they prefer. Only assessed using patients who completed both arms of the study (n=28).

2. Time (in Days) to Attain an Ideal BPS Score of Goal [3 weeks (ascertained at the end of period 1)]

   Proportion of patients in the study population estimated to reach a BPS at goal in the first period as a function of the time (in days) from day 1, presuming they were followed for 21 days and contributed a BPS score on each of those days. Constipation was graded using the Victoria Bowel Performance Scale (BPS), a nine-point scale from -4 (constipation) to +4 (diarrhea) which has been validated for use in patients receiving palliative care.

3. Incidence of Cramps [Last 18 days of each 21 day study period]

   The patients were asked to indicate any experience of cramps while on study treatment

4. Rectal Measures [Last 18 days of each 21 day study period]

   The patients were asked to indicate any experience of rectal bleeding or rectal pain while on study treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Adult patient (18 years and above) with diagnosis of cancer.

2. Patient requires treatment or prevention of constipation.

3. Patient is able to communicate effectively with staff.

4. Expected prognosis more than 12 weeks.

5. On or starting opioid therapy

Exclusion Criteria:

1. Patient unable to take oral medication.

2. Allergy or previous intolerance to PEG or sennosides.

3. Lactose intolerant.

4. Contraindication to PEG or sennosides.

5. Known or suspected bowel obstruction or ileus.

6. Colostomy or ileostomy.

7. Inflammatory bowel disease.

8. Hospitalisation expected within the study period.

9. Patient unable to complete the study diary in English.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BC Cancer Agency	Vancouver	British Columbia	Canada	V5Z 4E6

Sponsors and Collaborators

• British Columbia Cancer Agency

Investigators

• Principal Investigator: Philippa Hawley, FRCPC, British Columbia Cancer Agency

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 11, 2017

More Information

Publications

None provided.

• Responsible Party: Pippa Hawley, Principal Investigator, British Columbia Cancer Agency
• ClinicalTrials.gov Identifier: NCT01189409
• Other Study ID Numbers: H0901329
• First Posted: Aug 26, 2010
• Last Update Posted: Aug 28, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Pippa Hawley, Principal Investigator, British Columbia Cancer Agency: Constipation; Opioids; Cancer; Polyethylene glycol; Sennosides; Opioid Therapy
• Additional relevant MeSH terms: Constipation; Opioid-Induced Constipation; Sennosides

Study Results

Participant Flow

Arm/Group Title	PEG Then Senna	Senna Then PEG
Arm/Group Description	PEG in stepped bowel protocol PEG then Senna: Stepped bowel protocol with PEG for 3 weeks followed by senna for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).	Stepped bowel protocol with Senna then PEG Senna then PEG: Stepped bowel protocol with senna for 3 weeks followed by PEG for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).
Period Title: First 3 Weeks
STARTED	37	33
COMPLETED	19	23
NOT COMPLETED	18	10
Period Title: First 3 Weeks
STARTED	19	23
COMPLETED	13	15
NOT COMPLETED	6	8

Baseline Characteristics

Arm/Group Title	PEG Then Senna	Senna Then PEG	Total
Arm/Group Description	PEG in stepped bowel protocol PEG then Senna: Stepped bowel protocol with PEG for 3 weeks followed by senna for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).	Stepped bowel protocol with Senna then PEG Senna then PEG: Stepped bowel protocol with senna for 3 weeks followed by PEG for 3 weeks. Both active treatments accompanied by placebo of alternate (lactose powder).	Total of all reporting groups
Overall Participants	37	33	70
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 54.1%	22 66.7%	42 60%
>=65 years	17 45.9%	11 33.3%	28 40%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	72.8	59.2	66
Sex: Female, Male (Count of Participants)
Female	23 62.2%	15 45.5%	38 54.3%
Male	14 37.8%	18 54.5%	32 45.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Diagnosis (Count of Participants)
Lung	4 10.8%	6 18.2%	10 14.3%
Breast	9 24.3%	4 12.1%	13 18.6%
GI	3 8.1%	3 9.1%	6 8.6%
Brain	1 2.7%	0 0%	1 1.4%
Kidney	1 2.7%	0 0%	1 1.4%
Prostate	3 8.1%	3 9.1%	6 8.6%
Bladder	1 2.7%	0 0%	1 1.4%
Haematological	3 8.1%	5 15.2%	8 11.4%
Other	12 32.4%	12 36.4%	24 34.3%

Outcome Measures

1. Primary Outcome

Title	Bowel Performance Scale (BPS)
Description	Mean values of Number of Days with Satisfactory Bowel Movements Per Days of Treatment across time by treatment, derived from the mixed effects Poisson regression model. If the BPS rating on a day was -1, 0 or +1, the patient's bowel movement on that day was deemed to be satisfactory.
Time Frame	Last 18 days of each 21 day study period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Polyethylene Glycol (PEG)	Sennosides
Arm/Group Description	Those patients on PEG during either treatment period	Those patients on sennosides during either treatment period
Measure Participants	28	28
Period 1	0.659	0.534
Period 2	0.641	0.636

2. Secondary Outcome

Title	Patient Preference
Description	The patients will be asked to state which treatment period they prefer. Only assessed using patients who completed both arms of the study (n=28).
Time Frame	end of study (6 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Polyethylene Glycol (PEG)	Senna	No Preference
Arm/Group Description	Participants who completed both arms of the study and preferred PEG over Senna	Participants who completed both arms of the study and preferred Senna over PEG	Participants who completed both arms of the study and had no preference in treatment
Measure Participants	28	28	28
Count of Participants [Participants]	13 35.1%	13 39.4%	2 2.9%

3. Secondary Outcome

Title	Time (in Days) to Attain an Ideal BPS Score of Goal
Description	Proportion of patients in the study population estimated to reach a BPS at goal in the first period as a function of the time (in days) from day 1, presuming they were followed for 21 days and contributed a BPS score on each of those days. Constipation was graded using the Victoria Bowel Performance Scale (BPS), a nine-point scale from -4 (constipation) to +4 (diarrhea) which has been validated for use in patients receiving palliative care.
Time Frame	3 weeks (ascertained at the end of period 1)

Outcome Measure Data

Analysis Population Description

Patients with a minimum of 7 days of treatment in the first period were included in the modeling.

Arm/Group Title	Polyethylene Glycol (PEG)	Senna
Arm/Group Description	Patients on the stepped bowel protocol with PEG accompanied by placebo alternate for the first 3 weeks.	Patients on the stepped bowel protocol with Senna accompanied by placebo alternate for the first 3 weeks.
Measure Participants	23	24
Median (95% Confidence Interval) [Days]	6	8

4. Secondary Outcome

Title	Incidence of Cramps
Description	The patients were asked to indicate any experience of cramps while on study treatment
Time Frame	Last 18 days of each 21 day study period

Outcome Measure Data

Analysis Population Description

Patients who reported incidence of cramps at least once.

Arm/Group Title	Polyethylene Glycol (PEG)	Senna
Arm/Group Description	Patients on PEG during either treatment period	Patients on Senna during either treatment period
Measure Participants	70	70
Count of Participants [Participants]	27 73%	25 75.8%

5. Secondary Outcome

Title	Rectal Measures
Description	The patients were asked to indicate any experience of rectal bleeding or rectal pain while on study treatment
Time Frame	Last 18 days of each 21 day study period

Outcome Measure Data

Analysis Population Description

Patients who reported incidence of rectal pain or rectal bleeding at least once.

Arm/Group Title	Polyethylene Glycol (PEG)	Senna
Arm/Group Description	Patients on PEG during either treatment period	Patients on Senna during either treatment period
Measure Participants	70	70
Rectal Bleeding	7 18.9%	6 18.2%
Rectal Pain	10 27%	9 27.3%

Adverse Events

Time Frame	6 weeks (the end of the second treatment period)
Arm/Group Title	Polyethylene Glycol (PEG)		Senna
Arm/Group Description	Patients on PEG during either treatment period		Patients on Senna during either treatment period
All Cause Mortality
	Polyethylene Glycol (PEG)		Senna
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		1/70 (1.4%)
Serious Adverse Events
	Polyethylene Glycol (PEG)		Senna
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/70 (0%)		0/70 (0%)
Other (Not Including Serious) Adverse Events
	Polyethylene Glycol (PEG)		Senna
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/70 (8.6%)		7/70 (10%)
Gastrointestinal disorders
Diarrhea	4/70 (5.7%)		2/70 (2.9%)
Cramps	0/70 (0%)		1/70 (1.4%)
General disorders
Dysphagia	0/70 (0%)		1/70 (1.4%)
Pain	0/70 (0%)		1/70 (1.4%)
Dizziness	0/70 (0%)		1/70 (1.4%)
	1/70 (1.4%)		0/70 (0%)
Product Issues
Allergic Reaction	1/70 (1.4%)		0/70 (0%)
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	0/70 (0%)		1/70 (1.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.